Prophylactic cranial irradiation (PCI) significantly decreases risk of brain metastases in patients with bulky, higher stage small-cell urothelial cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 486-486 ◽  
Author(s):  
Seungtaek Choi ◽  
Matthew T Campbell ◽  
Amishi Yogesh Shah ◽  
Neema Navai ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Urothelial Cancer ◽  
Systemic Disease ◽  
Brain Mri ◽  
Prospective Trial ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Developing Brain

486 Background: Patients with bulky, higher-stage small cell urothelial cancer (≥T3b, N+, and/or M+) have a high risk of developing brain metastases. Siefker-Radtke et al reported a 50% risk of brain metastases in this patient population. Therefore, a prospective trial evaluating the potential benefit of PCI was undertaken. Methods: Thirty patients with stage ≥T3b, N+, and/or M+ disease (without brain metastases on MRI) were treated between 12/2008 and 5/2018 with PCI. Patients were treated to a total dose of 30 Gy in 2 Gy fractions over 3 weeks. The patient had baseline brain MRI and mini-mental status exam (MMSE) before the treatment began. After treatment, patients underwent MRI and MMSE every 3-4 months for one year and every 6 months thereafter. If the patients did not have M+ disease at diagnosis, they were also treated with neoadjuvant chemotherapy (usually consisting of cisplatin/etoposide alternating with Adriamycin/ifosfamide), followed by a radical cystectomy. The PCI was either given between the last cycle of chemotherapy and surgery or after the surgery. Both acute and chronic toxicity from PCI were measured using CTCAE 3.0. Change in the MMSE after PCI was evaluated using a t-test. Results: Twenty-nine patients were evaluable. Twenty-four patients had ≥T3b and/or N+ disease and 5 patients had M1 disease. Median follow-up was 22 months (range 8-103 months). Four patients have developed brain metastases with a median time of 11.5 months after PCI (range 3-23 months). Two of these patients have died. Nine other patients have died from progressive systemic disease, but they did not have evidence of brain metastases. PCI was well-tolerated, with no grade ≥2 toxicity seen. Acute grade 1 toxicity seen included headache, nausea, and dermatitis. MMSE were available for 19 patients with a median follow-up of 13 months (range 3-87 months). There was no significant change in the MMSE scores after the PCI when compared to baseline (p = 0.61). Conclusions: In this study, PCI decreased the risk of developing brain metastases in patients with bulky, higher-stage small cell urothelial cancer from 50% (historical) to 13.8% without significant toxicity. Clinical trial information: NCT00756639.

scholarly journals Role of Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer

2021 ◽  
Vol 19 (12) ◽  
pp. 1465-1469
Author(s):  
Nathan Y. Yu ◽  
Terence T. Sio ◽  
Vinicius Ernani ◽  
Panayiotis Savvides ◽  
Steven E. Schild
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Developing Brain ◽  
Small Cell Lung ◽  
Extensive Stage

Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study

2021 ◽  
pp. JCO.21.00639
Author(s):  
Núria Rodríguez de Dios ◽  
Felipe Couñago ◽  
Mauricio Murcia-Mejía ◽  
Mikel Rico-Oses ◽  
Patricia Calvo-Crespo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Free Recall ◽  
Brain Metastases ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Hippocampal Avoidance

PURPOSE Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

Should patients with extrapulmonary small cell carcinoma receive prophylactic cranial irradiation? An Irish experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2609-2609
Author(s):  
Jarushka Naidoo ◽  
Sandra Deady ◽  
Harry Comber ◽  
Paula Calvert
Keyword(s):  
Brain Metastases ◽  
Cell Carcinoma ◽  
Survival Data ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Disease Biology ◽  
Stage Disease ◽  
Extensive Stage ◽  
Extrapulmonary Small Cell Carcinoma

2609 Background: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease. Management is based on small cell lung carcinoma, and experience of disease biology on single institution studies. Prophylactic cranial irradiation (PCI) is not routinely administered in EPSCC. This study investigates the role of PCI in EPSCC, by analyzing the incidence, treatment and survival of patients with brain metastases in a national cohort. Secondary aims were to investigate disease biology and epidemiology. Methods: An audit was undertaken of patients diagnosed with primary EPSCC from the National Cancer Registry of Ireland, between 1995-2007. The number of patients who developed brain metastases, received cranial radiotherapy, and their survival data, were documented. Patient and disease characteristics, treatment, and survival data stratified by stage and primary site, were tabulated. Results: 280 patients were found. 141 (50.4%) patients were male, and 139 (49.6%) were female. 186 (66.4%) patients had extensive stage disease, 65 (23.2%) had limited stage disease, and in 29 (10.3%) patients the stage was not known. 17 patients (5.4%) developed brain metastases, 11 of which (64.7%) received cranial irradiation. These patients had a median progression-free survival (PFS) of 5.2 months, and a median overall survival (OS) of 10.2 months. The commonest primary sites were the oesophagus (n=43, 15.4%), cervix uteri (n=17, 6.0%), bladder (n=13, 4.6%) and prostate (n=10, 3.6%). There were 315 events of distant metastasis, and 21 local recurrence events. The commonest metastatic sites were the liver, 110 (34.9%), lymph nodes 58 (20.7%), lung 38 (12.1%), and bone 36 (12.8%). The median PFS and OS for limited stage EPSCC was 8.8 months and 14.9 months, and 1.5 months and 2.3 months for extensive stage EPSCC. Conclusions: Brain metastases were uncommon in this cohort (5.4%), and patients lived longer, suggesting a low rate of mortality from brain metastases. PCI is thus probably not warranted in EPSCC. Prospective data are necessary to support PCI in EPSCC. This is one of the largest datasets on EPSCC, providing insights into disease biology.

Thoracic twice-daily radiotherapy and brain metastasis in patients with small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8560-8560
Author(s):  
Haiyan Zeng ◽  
Rui Li ◽  
Chen Hu ◽  
Guoqin Qiu ◽  
Hong Ge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Small Cell Lung

8560 Background: Although thoracic twice-daily radiotherapy (TDRT) is one of standards of care for small cell lung cancer, its impact on brain metastases remains unknown. This study aimed to compare TDRT with once-daily radiotherapy (ODRT) for the brain metastases rate after prophylactic cranial irradiation in patients with small cell lung cancer. Methods: Consecutive patients received TDRT (45Gy/30f)/ODRT(50-66Gy/25-33f), chemotherapy and prophylactic cranial irradiation were retrieved from eight hospitals’ databases between 2003 and 2016. The endpoints included brain metastases, progression-free survival and overall survival. Brain metastases rate was evaluated using competing risk analysis. A 1:1 propensity score matching approach was used to control confounding between these two groups. Confounding covariates included eight demographic variables and eight treatment related covariates. Results: Of the 778 eligible patients with median age of 55-year (IQR, 48-61), 204 (26.2%) were female. At a median follow-up time of 23.6 months (IQR, 14.2- 38.2), 131 (16.8%) experienced brain metastases. The rates in TDRT were significantly higher than ODRT (3-year, 26.0% vs. 16.9%; HR = 1.55, 95%CI 1.06-2.26, P = 0.03). Of the 338 matched patients (169 in ODRT vs. 169 in TDRT), 60 (17.8%) experienced brain metastases with 3-year rate of 14.9% in ODRT vs 26.0% in TDRT (HR = 1.71, 95%CI 1.02-2.88, P = 0.04). Progression-free survival was similar in both the whole cohort and the matched one. Overall survival in ODRT tended to be significantly longer after matching (median, 47.2 months in ODRT vs. 32.8 months in TDRT; HR = 1.41, 95%CI 0.99-2.01, P = 0.06). When jointly evaluated biologically effective dose (BED), start of any therapy to the end of radiotherapy (SER) and TDRT/ODRT in the multivariable analysis, the impact of ODRT/TDRT on overall survival become more significant (HR = 1.69, 95%CI 1.05-2.71, P = 0.03). Conclusions: Patients with small cell lung cancer who were treated with thoracic TDRT appeared to have higher risk of brain metastases than those with ODRT, which strongly supports the need for further prospective randomized clinical trials, especially in China or other parts of Asia.

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